I've been wondering that same question ever since Rey Mysterio lost the World Heavyweight Championship at Great American Bash 2006. I mean, I've watched Rey Mysterio very closely ever since I started watching wrestling. Up until 2006, in WWE, Rey Mysterio was only given the Cruiserweight Championship and the WWE Tag Team Championship. He's competed for the WWE Championship and the United States Championship several times in the past, but always lost, and it give me the feeling that those were the only titles WWE would allow him to hold, because of his size.
Up until Wrestlemania 22, I thought that to be the World Heavyweight Champion, you had to be over the cut-off of a cruiserweight. Which I believe was about 215 pounds. Rey Mysterio is about 40 lbs. under that. When he won it, I thought to myself that WWE lowered the standards on who can win the World Heavyweight Title. Since then, Rey has won the Intercontinental Championship two times.
I can see Rey Mysterio getting World Heavyweight Championship matches, but I don't know if he'd win it. I mean, since losing it, Rey Mysterio hasn't had any push closely even near what he had in 2006. He's competed for the same title several times and never won it. The good thing about Rey Mysterio is that he doesn't always need the title to get over. The kids love watching him in the ring, and that's what really matters. I don't find it too likely for Rey to win the title again, but if they needed him, he's sure to be there.